Adult AIDS Clinical Trials Unit: Component C4: Developmental Pharmacology. This application seeks to extend the goals of the Core Pharmacology (Component C.2) Laboratory to include the following specific aims; 1. To establish a comprehensive program to investigate the clinical pharmacology of current and newly introduced drugs with potential value for the treatment of Human Immunodeficiency Virus (HIV) infection, opportunistic infections and malignancies. 2. To conduct clinical protocols specifically designed , or nested within larger studies, to investigate; clinically important drug interactions, pharmacokinetic/pharmacodynamic characteristics among subpopulations of HIV-infected individuals, the influence of concurrent disease on antiretroviral disposition.. 3. To integrate the results obtained from an in vitro hollow fiber perfusion model which correlates extracellular and intracellular concentrations of antiretroviral agents (parent and metabolites) with the development of clinical protocols to assess the potential mechanisms of implementing a therapeutic drug monitoring program to guide chronic anti- HIV therapy. 4. To investigate the extent of blood component distribution of antiretroviral agents and their relationship to determining the appropriate biologic matrix for future therapeutic drug monitoring studies. To achieve these aims a series of clinical and in vitro studies will be conducted with the overall goal of elucidating the relationship between serum concentrations. Intracellular concentrations and comparative assay methodologies to provide a basis for rational therapeutic drug monitoring for chronic anti-HIV therapy.